一项关于世界贸易中心粉尘暴露的FDNI消防员哮喘/慢性阻塞性肺疾病重叠预测的纵向研究
2018/11/02
摘要
背景：此前已知健康消防员接触世贸中心（WTC）粉尘而患有气道疾病。而这些刺激相关的哮喘/慢性阻塞性肺疾病重叠的危险因素并不清楚。
方法：该研究包括2137名WTC暴露的消防员，他们在2001年9月10日至2017年10月9日期间接受了支气管扩张肺功能试验（BD-PFT）。使用支气管剂后FEV1从基线哮喘中升高12%和200 ml诊断为哮喘，使用支气管扩张剂后FEV1/FVC比值低于0.7的诊断为COPD患者。符合这两个标准的参与者诊断为哮喘/慢性阻塞性肺疾病重叠。在2001年9月10日后和BD-PFT前进行血液筛查，测定血中嗜酸性粒细胞水平；参与者亚组中也有血清IgE和21种细胞因子测定（n＝215）。多个事件的边际Cox回归模型评估嗜酸性粒细胞水平或血清生物标志物与随后诊断的关联性，包括年龄、种族、吸烟、WTC暴露、911后第一次测定的FEV1/FVC比率和BMI作为协变量。
结果：BD-PFT诊断哮喘/慢性阻塞性肺疾病重叠99例（4.6%），孤立性哮喘202例（9.5%），孤立性COPD 215例（10.1%）。嗜酸粒细胞浓度超过300细胞/μl与哮喘/慢性阻塞性肺疾病重叠风险增加（HR：1.85，95% CI：1.16-2.95），但与孤立性哮喘或孤立性COPD无关。血清IL-4也预测哮喘/慢性阻塞性肺疾病重叠（HR：1.51倍的细胞因子浓度，95% CI：1.17-1.95）。较大的IL-21浓度与孤立性哮喘和孤立性COPD（HR：1.73，95% CI：1.27～2.35和HR：2.06，95% CI：1.31-3.23）相关。
结论：在WTC暴露的消防员中，升高的血液嗜酸性粒细胞和IL-4水平与随后出现的哮喘/慢性阻塞性肺疾病重叠有关。疾病特异的Th-2生物标志物在疾病诊断几年前提示患者有内在哮喘/慢性阻塞性肺疾病重叠的易感性。
Predictors of asthma/COPD overlap in FDNY firefighters with World Trade Center dust exposure: a longitudinal study.
Singh A, Liu C, Putman B, Zeig-Owens R, Hall CB, Schwartz T, Webber MP, Cohen HW, Berger KI, Nolan A, Prezant DJ, Weiden MD.
Abstract
BACKGROUND: Previously healthy firefighters with World Trade Center (WTC) dust exposure developed airway disease. Risk factors for irritant-associated asthma/COPD overlap are poorly defined.
METHODS: The study included 2,137 WTC-exposed firefighters who received a clinically-indicated bronchodilator pulmonary function test (BD-PFT) between 9/11/2001-9/10/2017. A post-BD FEV1 increase of >12% and 200 ml from baseline defined asthma, and post-BD FEV1/FVC ratio<0.7 identified COPD cases. Participants who met both criteria had asthma/COPD overlap. Eosinophil levels were measured on screening blood tests performed shortly after 9/11/2001 and prior to BD-PFT; a subgroup of participants also had serum IgE and 21 cytokines measured (N=215). Marginal Cox regression models for multiple events assessed the associations of eosinophil levels or serum biomarkers with subsequent diagnosis, with age, race, smoking, WTC-exposure, first post-9/11 FEV1/FVC ratio, and BMI included as covariates.
RESULTS: BD-PFT diagnosed asthma/COPD overlap in 99 individuals (4.6%), isolated-asthma in 202 (9.5%), and isolated-COPD in 215 (10.1%). Eosinophil concentration≥300 cells/μl was associated with increased risk of asthma/COPD overlap (HR: 1.85, 95% CI: 1.16-2.95), but not with isolated-asthma or isolated-COPD. Serum IL-4 also predicted asthma/COPD overlap (HR: 1.51 per doubling of cytokine concentration, 95% CI: 1.17-1.95). Greater IL-21 concentration was associated with both isolated-asthma and isolated-COPD (HR: 1.73, 95% CI: 1.27-2.35 and HR: 2.06, 95% CI: 1.31-3.23, respectively).
CONCLUSIONS: In WTC-exposed firefighters, elevated blood eosinophils and IL-4 levels are associated with subsequent asthma/COPD overlap. Disease-specific Th-2 biomarkers present years before diagnosis suggest patient-intrinsic predisposition to irritant-associated asthma/COPD overlap.
背景：此前已知健康消防员接触世贸中心（WTC）粉尘而患有气道疾病。而这些刺激相关的哮喘/慢性阻塞性肺疾病重叠的危险因素并不清楚。
方法：该研究包括2137名WTC暴露的消防员，他们在2001年9月10日至2017年10月9日期间接受了支气管扩张肺功能试验（BD-PFT）。使用支气管剂后FEV1从基线哮喘中升高12%和200 ml诊断为哮喘，使用支气管扩张剂后FEV1/FVC比值低于0.7的诊断为COPD患者。符合这两个标准的参与者诊断为哮喘/慢性阻塞性肺疾病重叠。在2001年9月10日后和BD-PFT前进行血液筛查，测定血中嗜酸性粒细胞水平；参与者亚组中也有血清IgE和21种细胞因子测定（n＝215）。多个事件的边际Cox回归模型评估嗜酸性粒细胞水平或血清生物标志物与随后诊断的关联性，包括年龄、种族、吸烟、WTC暴露、911后第一次测定的FEV1/FVC比率和BMI作为协变量。
结果：BD-PFT诊断哮喘/慢性阻塞性肺疾病重叠99例（4.6%），孤立性哮喘202例（9.5%），孤立性COPD 215例（10.1%）。嗜酸粒细胞浓度超过300细胞/μl与哮喘/慢性阻塞性肺疾病重叠风险增加（HR：1.85，95% CI：1.16-2.95），但与孤立性哮喘或孤立性COPD无关。血清IL-4也预测哮喘/慢性阻塞性肺疾病重叠（HR：1.51倍的细胞因子浓度，95% CI：1.17-1.95）。较大的IL-21浓度与孤立性哮喘和孤立性COPD（HR：1.73，95% CI：1.27～2.35和HR：2.06，95% CI：1.31-3.23）相关。
结论：在WTC暴露的消防员中，升高的血液嗜酸性粒细胞和IL-4水平与随后出现的哮喘/慢性阻塞性肺疾病重叠有关。疾病特异的Th-2生物标志物在疾病诊断几年前提示患者有内在哮喘/慢性阻塞性肺疾病重叠的易感性。
(中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校)
(Chest. 2018 Jul 17. pii: S0012-3692(18)31055-9. doi: 10.1016/j.chest.2018.07.002.)
(Chest. 2018 Jul 17. pii: S0012-3692(18)31055-9. doi: 10.1016/j.chest.2018.07.002.)
Predictors of asthma/COPD overlap in FDNY firefighters with World Trade Center dust exposure: a longitudinal study.
Singh A, Liu C, Putman B, Zeig-Owens R, Hall CB, Schwartz T, Webber MP, Cohen HW, Berger KI, Nolan A, Prezant DJ, Weiden MD.
Abstract
BACKGROUND: Previously healthy firefighters with World Trade Center (WTC) dust exposure developed airway disease. Risk factors for irritant-associated asthma/COPD overlap are poorly defined.
METHODS: The study included 2,137 WTC-exposed firefighters who received a clinically-indicated bronchodilator pulmonary function test (BD-PFT) between 9/11/2001-9/10/2017. A post-BD FEV1 increase of >12% and 200 ml from baseline defined asthma, and post-BD FEV1/FVC ratio<0.7 identified COPD cases. Participants who met both criteria had asthma/COPD overlap. Eosinophil levels were measured on screening blood tests performed shortly after 9/11/2001 and prior to BD-PFT; a subgroup of participants also had serum IgE and 21 cytokines measured (N=215). Marginal Cox regression models for multiple events assessed the associations of eosinophil levels or serum biomarkers with subsequent diagnosis, with age, race, smoking, WTC-exposure, first post-9/11 FEV1/FVC ratio, and BMI included as covariates.
RESULTS: BD-PFT diagnosed asthma/COPD overlap in 99 individuals (4.6%), isolated-asthma in 202 (9.5%), and isolated-COPD in 215 (10.1%). Eosinophil concentration≥300 cells/μl was associated with increased risk of asthma/COPD overlap (HR: 1.85, 95% CI: 1.16-2.95), but not with isolated-asthma or isolated-COPD. Serum IL-4 also predicted asthma/COPD overlap (HR: 1.51 per doubling of cytokine concentration, 95% CI: 1.17-1.95). Greater IL-21 concentration was associated with both isolated-asthma and isolated-COPD (HR: 1.73, 95% CI: 1.27-2.35 and HR: 2.06, 95% CI: 1.31-3.23, respectively).
CONCLUSIONS: In WTC-exposed firefighters, elevated blood eosinophils and IL-4 levels are associated with subsequent asthma/COPD overlap. Disease-specific Th-2 biomarkers present years before diagnosis suggest patient-intrinsic predisposition to irritant-associated asthma/COPD overlap.
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重症哮喘患者血液嗜酸性粒细胞的变异性
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重症嗜酸粒细胞性哮喘患者中的痰自身抗体
